Chloramphenicol is administered to infants and children with increasing frequency for nosocomial infections due to multiple resistant bacteria, and because of the increasing prevalence of invasive ampicillin-resistant H. influenzae infections. We, and other investigators, have found a wide interpatient variation in the pharmaco-kinetics of chloramphenicol in infants. A portion of the variability is accounted for by urinary loss of the prodrug, chloramphenicol succinate. We hypothesize that interpatient differences in the activity and mass of the hepatic drug disposition system is responsible for a portion of the variable pharmacokinetics. We therefore intend to assess this activity by measuring plasma antipyrine clearance, and urinary excretion o 6-Beta-hydroxycortisol and D-glucaric acid. The ontogeny of chloramphenicol metabolism will be defined. Quantitation of compounds studied will be by HPLC. We will also assess new methods of detecting early hematologic toxicity based on assaying enzymes involved in hemoglobin synthesis in blood. Rifampin is being administered to infants and children as a chemoprophylactic agent for H. influenzae infections, and (in combination with other antibiotics) for the treatment of infections of devices used in the treatment of hydrocephalus. We intend to define the appropriate oral rifampin dose for efficacious erradication of H. influenzae, and define the age dependency of metabolism. The pharmacokinetics after oral administration and the penetration into CSF will be determined in children treated with this drug for shunt infections. Antibiotics will be administered under control conditions, serum collected and parent drug and metabolites quantitated by HPLC. Auto-induction of clearance and interaction with anticonvulsant medications will be sought. Data derived from this research will allow the development of rational, scientifically-based guidelines for their use in infants and children.